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In the randomized, double-blind Women's Isoflavone Soy Health trial, long-term dietary soy isoflavone supplementation in a dose comparable to that of traditional Asian diets had no effect on global cognition in healthy postmenopausal women.

A total of 350 healthy postmenopausal women 45 to 92 years of age were allocated to daily treatment with 25 g of isoflavone-rich soy protein or a matched placebo containing milk protein. The isoflavone-rich soy protein contained 91 mg aglycone weight isoflavones (154 mg total isoflavone equivalents) composed of genistein (52 mg aglycone equivalents), daidzein (36 mg aglycone equivalents), and glycitein (3 mg aglycone equivalents). The primary study outcome was change in global cognition between treatment groups, calculated as an average of standardized scores for 14 neuropsychological tests administered at baseline and again after 2.5 years. Secondary outcomes compared changes in cognitive factors and individual tests.

Intention-to-treat analyses included information from 313 women with baseline and endpoint cognitive test data. There was no significant between-group difference for change from baseline in global cognition (mean standardized improvement of 0.42 in the isoflavone group and 0.31 in the placebo group; mean standardized difference 0.11, 95% CI −0.13–0.35). Secondary analyses indicated greater improvement on a visual memory factor in the isoflavone group (mean standardized difference 0.33, 95% CI 0.06–0.60) but no significant between-group differences in three other cognitive factors or individual test scores, and no significant difference within a subgroup of younger postmenopausal women.